This phase I/II trial tests the safety and side effects of psilocybin in combination with therapy for the treatment of patients with metastatic cancer and symptoms of anxiety and/or depression. Psilocybin is a substance being studied in conjunction with therapy for the treatment of anxiety and depression in patients with cancer. In this study, the psilocybin...
This phase I trial tests the safety and side effects of a second episode of psilocybin-assisted group therapy and how well it works in treating anxiety and distress in patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and had a partial response to their first retreat. Up to 50% of patient...
Psilocybin, a serotonin receptor agonist in the brain, significantly and quickly improves depressive symptoms while inducing profound acute subjective effects. The benefit-risk ratio of psilocybin in treatment-resistant depression seems favorable, but needs to be confirmed. Moreover, the role of 5-HT2A receptors, involved in the psychedelic experience, on th...
Chronic pain and mood disorders co-occur, exacerbate one another and share neurobiological mechanisms, but whether a single intervention could promptly alleviate both conditions remains unclear. Here, in two chronic pain models, we show that a single dose of psilocybin induces a rapid and sustained reversal of both mechanical allodynia and anxiodepression-li...
Abstract Classic serotonergic psychedelics engage 5-HT receptors throughout the nervous system, but how maternal exposure intersects with embryonic brain interfaces is poorly defined. Here we tested in mice whether maternally administered lysergic acid diethylamide (LSD) accesses embryonic cerebrospinal fluid (CSF) and whether embryonic choroid plexus (ChP) ...
BackgroundMajor depressive disorder (MDD) is a significant public health concern, and current treatments often have limitations in effectiveness and adherence. Psilocybin, a psychedelic compound found in certain mushrooms, is being explored as a potential treatment for depression. It primarily acts through the serotonin 5-HT2A receptor but interacts with 5-H...
Through its widespread reciprocal connections with the cerebral cortex, the claustrum is implicated in sleep and waking cortical network states. Yet, basic knowledge of neuromodulation in this structure is lacking. The claustrum is richly innervated by serotonergic fibers, expresses serotonin receptors, and is suggested to play a role in the ability of psilo...
Depression prevalence is markedly elevated in oncological patients, particularly among head and neck cancer (HNC) cohorts, who face twice the prevalence of major depressive disorder (MDD) compared to other cancer populations. MDD in this context independently predicts poorer clinical outcomes and increased morbidity. HNC management often involves acute surgi...
Depression, a common mental disorder, affects people at different stages of life.Classic antidepressant treatment is generally effective, however, it is prolonged.Nonetheless, numerous patients who undergo various classic antidepressant therapies still suffer from depression.Therefore, the search for novel medications is essential.In this review, we explore ...
Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impression...
The resurgence of psychedelic-assisted psychotherapy marks a pivotal evolution in mental health treatment, challenging traditional paradigms by integrating compounds such as psilocybin, LSD, MDMA, and ketamine into clinical practice. Historically marginalized due to regulatory and societal concerns, these agents are now gaining recognition for their unique n...
The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT2A serotonin receptor (5-HT2AR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety,...
Background and Hypothesis Visual hallucinations (VH) are a core symptom of both Lewy body diseases (LBDs; e.g., Parkinson’s disease and dementia with Lewy bodies) and serotonergic psychedelics (SPs; e.g., psilocybin and mescaline). While these classes of VH differ in etiology, shared pathways are suggested by overlapping phenomenology and neural mechanisms. ...
Major depressive disorder is a debilitating condition, with many patients unresponsive to conventional monoaminergic antidepressants. Rapid-acting antidepressants such as ketamine and psilocybin offer promising alternatives, relieving symptoms within hours. Ketamine, an NMDA receptor antagonist, and psilocybin, a serotonergic psychedelic primarily targeting ...
Background/Objectives: Hallucinogenic substances such as psilocybin, psilocin, ergometrine, ergotamine, and lysergic acid diethylamide (LSD) have been demonstrated to enhance the force of contraction (FOC), in part due to the phosphorylation of phospholamban in human atrial preparations via 5-HT4 serotonin receptors and/or H2 histamine receptors. However, wh...
In this study, we provide the first study to integrate molecular and functional neuroimaging during psychedelic drug effects in humans. Using simultaneous PET-MRI technology, we describe multiple brain actions of lysergic acid diethylamide (LSD) in healthy volunteers. We quantify the occupancy of LSD at cerebral serotonin 2A receptors and show that LSD incre...
Millions worldwide suffer from chronic pain, a complex condition often accompanied by depression and anxiety, highlighting the urgent need for innovative treatments. Classic psychedelics, including psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), primarily act on serotonin 5-HT2A receptors and have emerged as potential modulato...
4-Hydroxytryptamines such as psilocin and its prodrug psilocybin are of considerable current interest for innovative antidepressant and other neuropsychiatric treatments. We here present a synthetic route towards 4-hydroxytryptamines displaying a high versatility for SAR exploration at the aliphatic nitrogen. The core concept is to apply HATU-mediated amide ...
Psilocybin (active compound of "magic mushrooms") is a prototypical psychedelic substance that acts via agonism on serotonin (5-HT) 2A receptors. Psilocybin is rapidly metabolized into its active metabolite psilocin. Psilocybin is currently under investigation as potential treatment for various neuropsychiatric disorders. Psilocybin is also widely used for r...
Serotonin 5-HT2A receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been impli...
